Cardiac Stem Cell Niche, MMP9, and Culture and Differentiation of Embryonic Stem Cells

Mishra, Paras Kumar; Kuypers, Nicholas J.; Singh, Shree Ram; Leiberh, Noel Diaz; Chavali, Vishalakshi; Tyagi, Suresh C.

doi:10.1007/978-1-62703-508-8_13

Cited by 11 publications

(16 citation statements)

References 33 publications

(22 reference statements)

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“…Embryonic stem cells (ESCs) are totipotent, self-renewing, clonogenic and differentiate into a wide variety of cell types [65]. These cells are derived from mammalian embryos during the transition from totipotency, when individual blastomeres can make all cell lineages.…”

Section: Embryonic Stem Cellsmentioning

confidence: 99%

“…Both the stiffness of extracellular matrix (ECM) and surrounding niche/microenvironment play pivotal roles in ESC differentiation. Without optimal culture conditions or genetic manipulations embryonic stem cells rapidly differentiate in to other cells types [71] But it seems highly essential to understand the components which regulate ESC differentiation and unlock the regenerative potential of ESC-based therapies [65]. Stem cells isolated from blastocysts can be used for transplantation to find an option for the treatment of Parkinson,s disease and other neurodegenerative disease/disorder like Alzheimer disease.…”

Section: Embryonic Stem Cellsmentioning

confidence: 99%

“…Embryonic stem cells derived from oligodendrocyte progenitor are used in cell transplants for restoration of locomotion after spinal cord injury because these cells remyelinate [72]. ESC culture and differentiation require cell specific niche/microenvironment [65]. Niche is also formed by spindle shaped cells found on the surface of bone in the bone marrow.…”

Section: Embryonic Stem Cellsmentioning

confidence: 99%

“…Niche is also formed by spindle shaped cells found on the surface of bone in the bone marrow. Moreover, expression of tissue inhibitor of metalloproteinase-4 (TIMP4) in differentiating cells needs Matrix metalloproteinase-9 (MMP9) that induces fibrosis and causes stiffness of the ECM and impairs differentiation of cardiac stem cells into cardiomyocytes (Figure 6b) [65]. However, for clinical use various embryonic stem cell lines [73] have been derived from human blastocysts without destruction of human embryo [74,75].…”

Section: Embryonic Stem Cellsmentioning

confidence: 99%

“…Moreover, transcriptome analysis attuned to natural embryonic cardiogenesis provides a robust platform to probe coordinated cardiac specification and maturation from bioengineered stem cell-based model systems. Interestingly, matrix metalloproteinase-9 (MMP9) induces fibrosis that causes stiffness of the ECM and impairs differentiation of cardiac stem cells into cardiomyocytes [65]. It clears that stem cells possess enough therapeutic potential to cure cardiac diseases [153].…”

Section: Regeneration Of Diverse Cardiac Smooth Muscle and Endothelimentioning

confidence: 99%

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Role of regeneration in tissue repairing and therapies

Upadhyay¹

2015

J Regen Med Tissue Eng

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Present review article emphasizes role of regeneration mechanism in various tissues and its use in organ transplantation for wound healing and repairing. This article also explains uses of various stem cell types in transplantation technologies and its applications in regenerative medicine and therapeutics. This review also addresses tissue engineering methods and use of new biological scaffold materials and promising candidates such as immunomodulators, adhesions, integrins in tissue repairing and induction of regeneration in injured tissues. In addition, role of various molecules of immune cell system, gene cascades and transcription specific proteins (TSPs) and growth factors in formation of microenvironment for differentiation are also explained. Moreover, mechanism of regeneration in various tissues such as neural, skeletal, cardiac, muscular, adipose and gonadial tissues, and bone marrow is described in detail. This article also suggest an urgent need for development of new advanced methods, technologies, biomatrices, polymers and scaffold materials, and cell based therapies to overcome the problem of disable and injured patients. Hence, landmark innovations are required in the field of regenerative medicine, tissue engineering, and developmental biology for successful tissue repairing and organ transplants to serve the human society.

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Section: Embryonic Stem Cellsmentioning

confidence: 99%

Section: Embryonic Stem Cellsmentioning

confidence: 99%

Section: Embryonic Stem Cellsmentioning

confidence: 99%

Section: Embryonic Stem Cellsmentioning

confidence: 99%

Section: Regeneration Of Diverse Cardiac Smooth Muscle and Endothelimentioning

confidence: 99%

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Role of regeneration in tissue repairing and therapies

Upadhyay¹

2015

J Regen Med Tissue Eng

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Intracellular matrix metalloproteinase-9 mediates epigenetic modifications and autophagy to regulate differentiation in human cardiac stem cells

Yadav

Mishra

2021

Stem Cells

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Epigenetic reprogramming and autophagy have critical roles in differentiation of stem cells. However, very little is known about how epigenetic modifications are mediated and how they contribute to autophagy and differentiation in human cardiac stem cells (hCSCs). Previously, we have reported that intracellular matrix metalloproteinase-9 (MMP9), a collagenase, mediates cell death in hCSCs. Here, we investigated whether intracellular MMP9 mediates epigenetic modifications and autophagy in hCSCs. We created MMP9KO hCSCs and treated them with 5-azacytidine, an inhibitor of DNA methylation, and bafilomycin A1, an inhibitor of autophagosome degradation, and evaluated epigenetic modifications, autophagic flux, and differentiation. Our results showed compromised epigenetic modifications, reduced autophagy, and impaired differentiation in MMP9KO hCSCs.Remarkably, paracrine MMP9 supplementation restored epigenetic modifications but further reduced autophagy in MMP9KO hCSCs. We conclude that intracellular MMP9 is a critical mediator of epigenetic modifications and autophagy in hCSCs. Furthermore, the endocrine and paracrine effects of MMP9 vary for regulating autophagy in hCSCs. These novel roles of MMP9 are valuable for stem cell therapy.

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Generating Double Knockout Mice to Model Genetic Intervention for Diabetic Cardiomyopathy in Humans

Chavali

Nandi

Singh

et al. 2014

Methods in Molecular Biology

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Diabetes is a rapidly increasing disease that enhances the chances of heart failure twofold to fourfold (as compared to age and sex matched nondiabetics) and becomes a leading cause of morbidity and mortality. There are two broad classifications of diabetes: type1 diabetes (T1D) and type2 diabetes (T2D). Several mice models mimic both T1D and T2D in humans. However, the genetic intervention to ameliorate diabetic cardiomyopathy in these mice often requires creating double knockout (DKO). In order to assess the therapeutic potential of a gene, that specific gene is either overexpressed (transgenic expression) or abrogated (knockout) in the diabetic mice. If the genetic mice model for diabetes is used, it is necessary to create DKO with transgenic/knockout of the target gene to investigate the specific role of that gene in pathological cardiac remodeling in diabetics. One of the important genes involved in extracellular matrix (ECM) remodeling in diabetes is matrix metalloproteinase-9 (Mmp9). Mmp9 is a collagenase that remains latent in healthy hearts but induced in diabetic hearts. Activated Mmp9 degrades extracellular matrix (ECM) and increases matrix turnover causing cardiac fibrosis that leads to heart failure. Insulin2 mutant (Ins2+/-) Akita is a genetic model for T1D that becomes diabetic spontaneously at the age of 3-4 weeks and show robust hyperglycemia at the age of 10-12 weeks. It is a chronic model of T1D. In Ins2+/- Akita, Mmp9 is induced. To investigate the specific role of Mmp9 in diabetic hearts, it is necessary to create diabetic mice where Mmp9 gene is deleted. Here, we describe the method to generate Ins2+/-/Mmp9-/- (DKO) mice to determine whether the abrogation of Mmp9 ameliorates diabetic cardiomyopathy.

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Cardiac Stem Cell Niche, MMP9, and Culture and Differentiation of Embryonic Stem Cells

Cited by 11 publications

References 33 publications

Role of regeneration in tissue repairing and therapies

Role of regeneration in tissue repairing and therapies

Intracellular matrix metalloproteinase-9 mediates epigenetic modifications and autophagy to regulate differentiation in human cardiac stem cells

Generating Double Knockout Mice to Model Genetic Intervention for Diabetic Cardiomyopathy in Humans

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